PDF《The association between BMP4 gene》

2015 Gu et al.;

licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Gu et al. Journal of Translational Medicine (2015) 13:14 DOI 10.1186/s12967-014-0368-x Genetic variants in BMP4, in the form of single nu- cleotide polymorphisms (SNPs), may result in a qualitative or quantitative change in the local production of BMP4 or in its effectiveness via its cognate receptor [20]. Although many mutations within BMP4 leading to various pheno- types have been reported [21], the single nucleotide poly- morphism of 6007C >

T (rs17563) of BMP4 is the only identified polymorphism in the coding region [22]. To date, there is no study regarding the association between BMP4 gene polymorphism and LVH incidence. Given the association between BMP4 and cardiac re- modeling [19], we postulate that the BMP4 gene poly- morphism may also affect the cardiac remodeling. In this study, we enrolled essential hypertentive patients with and without LVH, to test this hypothesis. Methods Enrollment A total of

1265 patients diagnosed with EH were recruited in our hospital from July

2007 to March 2012. All patients were assigned into LVH+ (EH with LVH) and LVH- (EH without LVH) groups based on the presence or absence of LVH. A complete medical history was obtained from all subjects, including diabetes mellitus (DM), alcohol intake, cigarette smoking, weight, height, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The study protocol was approved by the ethics committee of Nanjing University of Chin- ese Medicine. All patients provided an informed written consent. We measured total cholesterol (TC), total trigly- ceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatine kinase (CK), creatine kinase-MB (CK-MB), troponin T (TNT), fasting blood glucose (FBG), blood urea nitrogen (BUN), and serum creatinine [23]. Measurement of LVH The echocardiography was performed in three cardiac cycles at end diastole and end systole, by the two investi- gators who were blind to the genotypes of the patients using a HewlettCPackard imaging system (Sonos

2500 model, California). All measurements LV mass (LVM) was calculated at end-diastole using the formula: 0.8 * 1.04[(IVSd + LVIDD + PWTd) ? LVIDD] + 0.6 (IVSd: in- terventricular septal thickness, PWTd: posterior wall thickness, LVIDD: LV end-diastolic internal dimension), which yields values closely related (R = 0.90) to necropsy LV weight. LVM was divided by height 2.7 to obtain LVMI (LVM index). LVH was defined as LVMI >

49.2 g/2.7 m for men and >

46.7 g/2.7 m for women [13]. Genotyping of BMP4 gene DNA was extracted from peripheral whole blood using a Qiagen DNA Isolation Kit (Qiagen, Valencia, CA, USA). The specific product of the BMP4 gene was amplified by polymerase chain reaction (PCR) with primers 5'

-biotion- TGAAGGCAAGATGTCTGA- CACA-3'

(forward) and 5'

-CCTTCCTGCATTTCTATCCTA-3'

(reverse) for -5826 G >

A (rs1957860), and 5'

-ATTGCCCAACCCTGAGCT ATC-3'

(forward) and 5'

-biotin-TGGGGGCTTCATAACC TC-3'

(reverse) for 6007C >